Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

Okeke, Malachy I.; Okoli, Arinze S.; Diaz, Diana; Offor, Collins; Oludotun, Taiwo G.; Tryland, Morten; Bøhn, Thomas; Moens, Ugo

The discovery that VACV can be used as a vector to express heterologous transgenes in mammalian cells [28, 29] , the potential that VARV can be deployed as an agent of bioterrorism [30] and the increasing zoonotic potential of many orthopoxviruses (OPVs) especially VACV [31] , CPXV [32] and monkeypox virus (MPXV) [33] lead to the resurgence of poxvirus research (especially vaccine development) after the eradication of smallpox. Recombinant vaccines based on poxvirus are good candidates for prophylactic and therapeutic vaccination of humans and animals against infectious diseases and neoplasms [26, [34] [35] [36] . Poxviruses are suitable as vaccine vectors because they are thermostable, can infect different hosts and cell types, multiply only in the cytoplasm of infected cells and have capacity for insertion and expression of up to 25 kbp of foreign DNA as well as ease of scalability for commercial production. Among OPV-vectored vaccines, only Raboral V-RG (RVG), a recombinant rabies vaccines based on VACV has been registered. RGV was used to vaccinate against rabies in raccoons and foxes in North America and Europe [37, 38] . Except as an oncolytic agent, multiplication competent poxvirus vaccines are not recommended for vaccination (particularly in humans) due to the risk of adverse effects [39, 40] . Multiplication incompetent poxvirus vectors have been developed as a safer alternative to multiplication competent vectors and these include MVA, attenuated VACV Copenhagen (NYVAC) and attenuated derivatives of fowlpox virus (TROVAC) and canarypox virus (ALVAC). These multiplication deficient poxvirus vectors form the backbone of most poxvirus-vectored vaccines that are in preclinical development, clinical trials or under marketing authorization application (MAA) evaluation [26, 41] .